Calcium Pyrophosphate Arthritis Research Articles

Prevalence and factors associated to calcium pyrophosphate arthritis in patients with gout

Aim: To ascertain the prevalence of calcium pyrophosphate arthritis (CPPA) at diagnosis and during follow-up of patients with gout. Methods: Inception cohort of patients with gout prospectively recruited and followed-up from 1994–2023. Gout-case was defined as crystal-proved tophus or arthritis, or the presence of tophus plus double contour with ultrasonography. CPPA was defined as the presence of intra-leukocyte calcium pyrophosphate (CPP) crystals in synovial fluid (SF) and neat chondrocalcinosis in plain radiographs. Age, gender, time from onset of symptoms, number of flares, joint distribution, previous and prescribed treatments, colchicine prophylaxis, comorbidities, alcohol intake, use of diuretics, renal function, and previous vascular disease were available for analysis. Results: A total of 1,544 patients with gout, with an average of 4-year follow-up, were available for analysis. CPPA was observed in 127/1,544 cases (8.2%). In 37/1,544 patients (2.4%) CPP and monosodium urate (MSU) crystals were observed in the same SF sample at gout diagnosis, and 90/1,544 (5.8%) showed CPP crystals apart from the diagnosis of gout. CPPA-gout cases had more flares per year, but no more frequent polyarticular distribution at baseline compared to non-CPPA-gout. CPPA-gout cases were older at baseline and showed lower renal function. Women, patients using diuretics, patients with hypertension, and those with previous vascular events showed CPPA more frequently. Multivariate analysis showed that only age and use of diuretics were independently associated with CPPA, as other variables apparently associated were dependent on aging. Interestingly, an analysis of the prevalence in the three decades available showed an increased CPPA diagnosis through time, probably associated with increased awareness of the association. Conclusions: (1) CPPA is not infrequent in patients with gout; (2) it is associated with aging and diuretic use; (3) awareness of this association may increase the rate of diagnosis.

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies.

Calcium pyrophosphate deposition disease is categorized into radiographic chondrocalcinosis, acute calcium pyrophosphate arthritis, chronic calcium pyrophosphate arthritis, and osteoarthritis with calcium pyrophosphate deposition. These entities collectively are characterized by the deposition of calcium into joints, which then may cause localized and systemic inflammation, resulting in pain and swelling in the affected joints. Patients with the ANKH gene are more susceptible to the development of CPP arthritis as are those with primary hyperparathyroidism, hypomagnesemia, and hemochromatosis. Radiographic chondrocalcinosis is asymptomatic. Acute calcium pyrophosphate arthritis results in self-limited periods of joint pain and swelling in the affected joint. Along with localized inflammation, there may also be systemic inflammation characterized by fever and elevated inflammatory markers. Chronic calcium pyrophosphate arthritis results in periods of quiescence interrupted by flares that are identical to acute periods of disease. Osteoarthritis associated calcium pyrophosphate arthritis presents with chronic pain well described in osteoarthritis with periods of acute flares. In 2023, a joint effort by the American College of Rheumatology and the European League Against Rheumatism developed guidelines meant to aid in the recognition of calcium pyrophosphate deposition diseases. The diagnosis is made if there is proof of either crowned dens syndrome or synovial fluid analysis demonstrating calcium pyrophosphate crystals or when more than 56 points are summed utilizing the criteria described in the guidelines. Radiographic chondrocalcinosis requires no therapy. Acute calcium pyrophosphate arthritis is treated with the goal of aborting the flare. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, oral corticosteroids, parenteral corticosteroids, intraarticular corticosteroids, IL-1 inhibitors, or parenteral adrenocorticotropic hormone (ACTH). The goal in treatment for chronic calcium pyrophosphate arthritis is the suppression of acute flares. The drugs used for acute flare treatment may be given as maintenance therapy with the additional options of methotrexate and hydroxychloroquine.

Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review

Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising.

Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis

Aims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis nor CPP crystals in synovial fluid. Patients and controls with hemochromatosis or primary hyperparathyroidism were not included. Mutations of hemochromatosis genes (HFE), magnesium (Mg), calcium (Ca), phosphate, iron (Fe), transferrin saturation, ferritin, parathyroid hormone (PTH), and calcifediol levels were studied. Results: Three hundred patients and 300 sex and age matched controls were compared. Lower serum Mg (sMg) and higher ferritin levels were found among patients. Hypomagnesemia (HypoMg) and HFE mutations were more frequent among patients. Involvement of over one joint was observed in 199 (66.4%) patients whereas persistent joint inflammation was retrieved in 154 (51.4%) of the patients. Initial analysis showed that the frequency of polyarticular and inflammatory phenotypes seemed to be progressively overrepresented in patients with HFE mutations. Further bivariate and multivariate analysis adjusted for the time from onset disclosed that the presence of genotypes with C282Y mutations was associated with polyarticular disease (hazard risk 3.501, 95% confidence interval 1.862–6.581, P < 0.001). Although C282Y mutations also seemed to be associated with inflammatory patterns, the association did not reach statistical significance (P = 0.173). Conclusions: Low sMg and high ferritin levels are associated with CPP arthritis (CPPA). In patients without hemochromatosis, HFE mutations, and specifically C282Y mutations seem to associate with the polyarticular disease phenotype, and plausibly with the chronic inflammatory phenotype.

Prevalence and factors associated to diffuse idiopathic skeletal hyperostosis in gout

Aim: To evaluate the prevalence, associated factors, and the impact of diffuse idiopathic skeletal hyperostosis (DISH) in patients with gout. Methods: Patients with gout entering into an inception cohort were evaluated for either spinal or peripheral hyperostosis from January 2022 to April 2023. Age, gender, along with comorbid conditions associated to gout and DISH were analyzed, including the presence either axial or peripheral hyperostosis and associated calcium pyrophosphate arthritis (CPPA). Results: The prevalence of DISH was 25.6% (31/121) patients, neat peripheral joint hyperostosis affecting 51.6% (16/31). CPPA was also present in 11.6% (14/121) patients. Only older age and male gender were independently associated to the presence of DISH. The presence of hyperostosis in peripheral joints was not associated to a worse initial evaluation of the severity of gout. Conclusions: The presence of DISH in patients with gout seems to be related mostly to aging. Conditions apparently associated to DISH in gout patients seem therefore to be related to aging.

The role of dual energy computed tomography in the differentiation of acute gout flares and acute calcium pyrophosphate crystal arthritis

ObjectivesTo analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD).MethodsThirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition.ResultsSensitivity of DECT for gout was 63% (95% CI 0.41–0.81) with a specificity of 92% (0.41–0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23–0.83) and 92% (0.74–0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73–0.99) and a specificity of 83% (0.52–0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59–1.00) and 92% (0.74–0.99), respectively.ConclusionDECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis.Key Points• DECT offers a lower sensitivity for acute gout flares than previously described.• DECT sensitivity for acute CPP crystal arthritis is less than the already validated ultrasound.

POS1150 ANATOMICAL LOCATIONS AND CORRELATES OF CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITS OF THE SPINE – PATHOLOGIC EXAMINATION OF 77 SURGICAL CASES

Background:Spinal involvement in calcium pyrophosphate deposition disease (CPPD) is thought to be a rare occurrence and is seen infrequently as crowned dens syndrome. Furthermore, data on anatomical locations and correlates of calcium pyrophosphate (CPP) deposits in spinal CPPD are scarce.Objectives:To describe the anatomical locations and correlates of pathologically confirmed CPPD of the spine.Methods:Consecutive patients with spinal CPPD were identified via retrospective chart review of individuals who underwent spine surgery for intractable chronic neck or back pain at Massachusetts General Hospital between 2009 and 2014. These deposits and surrounding anatomical structures were surgically resected and confirmed to have calcium pyrophosphate deposition upon pathologic review. We reviewed musculoskeletal imaging (CT, MRI, XR) and laboratory data from these pathologically confirmed cases.Results:From April 2009 to August 2014, we identified 77 individuals with pathologically confirmed CPPD of the spine. The mean age was 68 years; 41 (53%) were female; mean BMI was 28.7. Calcium pyrophosphate (CPP) was grossly identified intraoperatively by the surgeon in 38 cases (50%), typically as “chalky white deposits” (Figure 1). CPP deposits were seen most frequently in the ligamentum flavum (23%) and intervertebral disc (23%), followed by other less common locations (Table 1). Imaging findings in the soft tissue or intervertebral disc suggestive of CPPD were found in 5 cases (6%), whereas findings of spinal canal narrowing, facet arthropathy, or ligamentum flavum thickening were eventually correlative with CPP deposits in pathologic specimens. Only 7 (9%) experienced a prior episode of acute CPP arthritis (pseudogout). Chondrocalcinosis on x-ray was seen in 26 cases (34%), most commonly in the wrist and/or knees. Osteoarthritis was present in all spinal imaging, and 65% had comorbid scoliosis. Laboratory abnormalities associated with secondary causes of CPPD (hypercalcemia, hypomagnesemia, hyperparathyroidism) were not seen with spinal CPPD.Conclusion:Spinal CPPD may occur more frequently than previously perceived. The ligamentum flavum and intervertebral discs were common anatomical locations for spinal CPPD. Advanced imaging of the spine showed low sensitivity for detecting spinal CPPD. Only a small minority had typical peripheral joint involvement or imaging with peripheral joint chondrocalcinosis. Thus, without pathologic confirmation, the vast majority of cases would remain unidentified. These findings call for the need to seek pathologic confirmation to determine the robust epidemiology and also raise the potential role for preoperative CPPD treatment.Table 1.Spinal Anatomic Locations of Pathologically Confirmed CPPDSpinal Anatomic LocationNo. of Sites (%)*ligamentum flavum29 (23)Intervetebral Disc28 (23)Other Location19 (15)Posterior Elements18 (15)Facet14 (11)Synovium8 (6)Interspinous Ligament3 (2)Subarticular/Lateral Recess2 (2)Fibrocartilaginous Tissue1 (1)Inner Spine1 (1)Other Ligament1 (1)*Some patients had more than one anatomic location where CPP was isolatedFigure 1.Gross visualization of calcium pyrophosphate deposition (black arrow)Disclosure of Interests:Jonathan Dau: None declared, Gary Ho: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, Vaxart, Grant/research support from: Ironwood, Horizon, Joseph Schwab: None declared, Minna Kohler Speakers bureau: Eli Lily, Consultant of: Novartis.

Efficacy and tolerance of anakinra in acute calcium pyrophosphate crystal arthritis: a retrospective study of 33 cases

Calcium pyrophosphate (CPP) deposition is a frequent joint disease with increased prevalence in older people in whom treatment of acute CPP arthritis with conventional therapies such as colchicine or non-steroidal anti-inflammatory drugs could be contraindicated or not used at an optimal dose. As recommended in gout, anakinra might represent an alternative treatment for arthritis. We aimed to analyze the efficacy and safety of anakinra in acute CPP arthritis in a large reported series. We retrospectively included all patients receiving anakinra for acute CPP arthritis between January 2011 and 2017. The following data were collected before and 4days after the first anakinra injection: swollen joint count (SJC), tender joint count (TJC), pain score on a visual analog scale (VAS, 0-100mm), and C-reactive protein (CRP) level. A good response was defined according the evaluation of the physician. We included 33 patients (24 women; mean age 79.2 ± 12.8years). The number of good responders was 27 (81.8%). At day 4, patients showed decreased mean VAS pain score (from 64.8 ± 26.5 to 21.2 ± 19.7mm, p < 0.0001), TJC (5.8 ± 5.0 to 1.0 ± 1.0, p < 0.0001), SJC (3.9 ± 2.7 to 0.9 ± 1.0, p < 0.0001), and CRP level (116.1 ± 71.6 to 26.0 ± 23.1mg/l, p < 0.0001). Anakinra was well tolerated, without skin complications. Only one patient had pneumonitis that was resolved with oral antibacterial agents. Anakinra could be a relevant alternative for managing acute CPP arthritis when conventional therapies are ineffective or contraindicated.

Acute Calcium Pyrophosphate Arthritis after Parathyroidectomy

Acute Calcium Pyrophosphate Arthritis after Parathyroidectomy

A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis.

IntroductionThe performance of ultrasound (US) in the diagnosis of acute gouty (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well defined. Most studies evaluated US as the basis for diagnosing crystal arthritis in already diagnosed cases of gout and few prospective studies have been performed.MethodsOne hundred nine consecutive patients who presented an acute arthritis of suspected microcrystalline arthritis were prospectively included. All underwent an US of the symptomatic joints(s) and of knees, ankles and 1st metatarsopalangeal (MTP) joints by a rheumatologist “blinded” to the clinical history. 92 also had standard X-rays. Crystal identification was the gold standard.ResultsFifty-one patients had MSU, 28 CPP and 9 had both crystals by microscopic analysis. No crystals were detected in 21. One had septic arthritis. Based on US signs in the symptomatic joint, the sensitivity of US for both gout and CPP was low (60 % for both). In gout, the presence of US signs in the symptomatic joint was highly predictive of the diagnosis (PPV = 92 %). When US diagnosis was based on an examination of multiple joints, the sensitivity for both gout and CPP rose significantly but the specificity and the PPV decreased. In the absence of US signs in all the joints studied, CPP arthritis was unlikely (NPV = 87 %) particularly in patients with no previous crisis (NPV = 94 %). X-ray of the symptomatic joints was confirmed to be not useful in diagnosing gout and was equally sensitive or specific as US in CPP arthritis.ConclusionsArthrocenthesis remains the key investigation for the diagnosis of microcrystalline acute arthritis. Although US can help in the diagnostic process, its diagnostic performance is only moderate. US should not be limited to the symptomatic joint. Examination of multiple joints gives a better diagnostic sensitivity but lower specificity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0701-7) contains supplementary material, which is available to authorized users.

Nonpharmacologic and Pharmacologic Management of CPP Crystal Arthritis and BCP Arthropathy and Periarticular Syndromes

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care.

THU0508 Incidence of Inflammatory Joint Diseases in Northern Savo Area in Finland in 2010

BackgroundMonitoring of the incidence of inflammatory joint diseases may provide new insight into the etiology of these diseases.ObjectivesAll rheumatologists practising in the Northern Savo rheumatological outpatient departments collected data on...

Chondrocalcinose

Definitive diagnosis of chondrocalcinosis (CC) is allowed by identification of calcium pyrophosphate (CPP) crystals in synovial fluid. In daily practice, X-Rays are the most frequent imaging used to detect CC. Most cases of CC are sporadic. If CC occurs before 60 years of age, primary metabolic disorders such as hyperparathyroidism, hypomagnesemia, and hemochromatosis or a familial predisposition should be particularly considered. Treatment of CPP arthritis includes application of ice, rest, joint aspiration and intra-articular injection of corticosteroids. Oral NSAIDs can be used cautiously, in particular in the elderly. Prophylaxis against frequent recurrent acute CPP crystal arthritis can be achieved with low-dose oral colchicine.